Interestingly the virulence of HBV may adaptively evolve thu
Interestingly, the virulence of HBV may adaptively evolve, thus affecting the macroscopic propagation of hepatitis B. Higher virulence in vivo may result in a higher transmission rate and mortality. By assuming that the transmission rate is a monotonically increasing function of virulence, , we propose another HBV infection model by linking population dynamics with evolutionary dynamics of HBV virulence, which is given bywhere the invasion fitness of mutant HBV infections, , is given byHere, denotes the speed of evolutionary adaptation. This model can reveal the impact of Benzoylmesaconitine of HBV virulence on the epidemic trend of hepatitis B. Besides, this coupled model also describe the impact of macroscopic propagation dynamics on the evolution of HBV virulence, which may provide a novel insight for the prevention and treatment of hepatitis B.
Funding This work was supported by the National Natural Science Foundation of China [grant numbers 11571272, 11631012]; the National Science and Technology Major Project of China [grant number 2012ZX10002001]; the Natural Science Foundation of Shaanxi Province [grant number 2015JQ1011]; and the China Postdoctoral Science Foundation [grant number 2014M560755].
Conflicts of interest
Introduction Hepatitis B virus (HBV) infection is a major global health problem, which affects 257 million people worldwide. It has been reported that 75% of HBV-infected people are Asian while it only has a lower prevalence (0.3%–1.5%) in Western countries. Despite significant progress has been made over the past decades, HBV-induced liver cirrhosis still represents a major health burden, and the risk of developing hepatocellular carcinoma (HCC) significantly increases in patients with chronic hepatitis B and type B-related liver cirrhosis [, , , ]. It is estimated that over 1.3 million deaths have been yearly reported from complications of liver cirrhosis, liver failure and HCC. Over 12% of patients with HBV cirrhosis die of liver failure, and up to 10% perish from HCC [, , , ]. Although many studies have attempted to understand the physiological, cellular, and molecular mechanisms of the hepatitis diseases, the pathogenesis of which is not fully understood. Liver progenitor cells, named as oval cells in rodents, are thought to be localized in canals of Hering and exhibit bipotential differentiation into both hepatocytes and cholangiocytes [9,10]. Recent studies showed that expansion of oval cells was observed in human chronic liver diseases, including HBV cirrhosis [, , , , ]. And in HBV induced liver damage, activated immune response impaired the regeneration of hepatocytes regardless of hepatic progenitor cells [16,17]. In addition, a fibrogenic response and the severity of liver diseases was positively correlated with the activation of oval cells [, , , ]. Furthermore, reports have documented that stem/progenitor cells might be the cell origins of HCC. Indeed, detailed immunophenotyping of human liver cancers revealed that they expressed progenitor cell markers [22,23]. Importantly, animal studies further showed that oval cells were involved in the formation of liver tumors in rodent models [, , , ] and the data from our lab also showed that hepatic progenitor cells might play a role in combined hepatocellular cholangiocarcinoma development . Taken together, all these facts suggest that oval cells is tightly related to HBV associated diseases. However, few reports elucidate the role of oval cells in HBV transgenic animal models [29,30]. So identification of key genes and biological pathways responsible for oval cell activation induced by HBV infection will improve our understanding of oval cell biology and HBV-related cirrhosis and hepatocarcinogenesis.
Materials and methods